7. PROJECT SUMMARY/ABSTRACT Half of those living with HIV in the U.S. are or will soon be >50 years of age. Heart failure, which has one of the highest disease burdens of any age-related condition nationwide, may soon become the most costly HIV- related comorbidity in terms of premature mortality, suffering, and healthcare expenditures. Many of its known risk factors are common to HIV-infected and uninfected individuals alike, but less is known about its pathogenesis in the context of suppressive HIV therapy. New evidence suggests that long-term survival with HIV is associated with greater risks for systolic and diastolic dysfunction as well as resultant heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Against a background of high diabetes, hypertension, and obesity risk in minority groups affected disproportionately by HIV, a unique set of etiologic and prognostic factors for heart failure in the context of HIV infection likely exists. The proposed research is a set of epidemiologic studies characterizing the role of HIV infection in heart failure incidence and survival, based on data from the largest HIV care provider in the Bronx, NY. Aim 1 will assess the association between HIV infection and heart failure incidence, and Aim 1b will identify risk factors, including major comorbidities, that may lead to greater mortality in optimally treated HIV-infected heart failure patients compared with HIV-uninfected heart failure patients. Aims 2 and 3 will implement machine learning methods within our longitudinal electronic medical record database to construct prediction models identifying HIV+ patients at greatest risk of developing HF, and to identify unique HIV-specific phenotypes of HFpEF and HFrEF. Prediction models developed in our clinical population (90% minority, 40% female) will be validated in a demographically complementary HIV+ cohort in Chicago (50% minority, 15% female) to evaluate the transportability of these models across patient populations. This award will provide ample training opportunities for the candidate to continue his progression to an independent academic research career with specialized experience at the intersection of HIV, cardiovascular disease, and medical informatics. Established institutional resources and a mentoring team with a proven record of success, as well as research conducted within a geographic area with endemic levels of HIV and heart disease, provide an ideal setting to successfully produce high quality research with major impact. The collaboration will establish a program for large-scale translational research in HIV and heart failure by developing a shared research platform between two major research institutions in the Bronx and Chicago.